Assessment of iron deficiency in the context of the obesity epidemic: importance of correcting serum ferritin concentrations for inflammation.
The correction of serum ferritin (SF) concentrations for inflammation because of infectious or parasitic diseases was recently proposed, especially in developing countries, but in many countries, adiposity has become the main cause of inflammation. We assessed, overall and by adiposity status, the bias in the estimation of iron deficiency (ID) on the basis of uncorrected SF. A cross-sectional survey in 2010 in Rabat-Salé, Morocco, used a random sample of 811 women aged 20-49 y. Adiposity was assessed by body mass index (BMI) (in kg/m²) (normal: BMI <25; overweight: BMI ≥25 to <30; obese: BMI ≥30), waist circumference, and body fat. Inflammation was indicated by a C-reactive protein (CRP) concentration >2 mg/L. ID was indicated by an SF concentration <15 μg/L. The correction factor of SF for inflammation was derived from our sample. Differential effects of SF correction on ID status on the basis of adiposity were assessed by models that included adiposity × correction interactions and accounted for the within-subject correlation. The prevalence of overweight was 33.0% and of obesity was 34.0%. Inflammation (42.3%) was strongly linked with adiposity (20.1%, 37.6%, and 68.4% in normal, overweight, and obese subjects, respectively; P < 0.0001). SF increased from a CRP concentration >2 mg/L. The correction factor of SF was 0.65. The prevalence of ID (37.2% compared with 45.2%; difference -8.0%, P < 0.0001) was underestimated by not correcting SF, and the difference increased with adiposity (-2.9%, -8.5%, and -12.4% in normal, overweight, and obese subjects, respectively; P-interaction < 0.0001). Analogous results were observed for other adiposity measures. In developing countries where ID remains prevalent but rates of obesity are already high, corrected SF should be used when assessing ID status, even if infectious or parasitic diseases are no longer widespread. This trial was registered at clinicaltrials.gov as NCT01844349.


Methodology and tools for source term assessment in case of emergency.
By looking at the power plant state of fission product barriers and critical safety systems, the magnitude of a potential radioactive release could be predicted in a timely manner to allow emergency response to be executed even before the occurrence of a release. This is the perspective in which the development of ASTRID methodology and tool is performed. The methodology maps out, for several reactor types as well as reactor containments, relevant process parameters and indicators, what and how to calculate and a structured way to summarise and conclude on potential source term and likely time projections. A computer tool is proposed to support the methodology, to suite different user situations, both on-site and off-site as well as size of staff, priority and work order. The output from such an assessment is intended to, first, give bases for decisions on necessary urgent protective actions pre-release, and, second, an input for the sophisticated dispersion calculation codes.


Distribution of hantavirus serotypes Hantaan and Seoul causing hemorrhagic fever with renal syndrome and identification by hemagglutination inhibition assay.
An epidemiologic evaluation of patients with hemorrhagic fever with renal syndrome from different locations in the People's Republic of China was conducted to define the prevalence of two Hantavirus serotypes, Seoul (SEO) and Hantaan (HTN). Serum specimens were collected between 5 and 14 days after the onset of illness and were tested for antibodies by both hemagglutination inhibition (HI) and plaque reduction neutralization (PRN). By the HI test, the geometric mean titer (GMT) of antibodies to SEO in the sera from individuals from Kaifeng City of Henan Province was five times higher than that to HTN. In contrast, by the HI test, the sera from individuals from Jiande County of Zhejiang Province had a GMT of antibodies to HTN that was seven times higher than that to SEO. In the sera from individuals from Shanghai, only a twofold difference was observed in HI antibody titers to the two hemagglutinins by the HI test, with that to HTN being higher than that to SEO. By the PRN test, the GMT ratios of antibody between HTN and SEO strains from individuals in Kaifeng, Jiande, and Shanghai were found to be 1:13, 14:1, and 2:1 respectively. A close correlation (r = 0.8219) and concordance rate (78.3%) were observed between the PRN and HI tests for the identification of the serotypes of individual cases of hemorrhagic fever with renal syndrome. The hantavirus serotypes from individuals in Kaifeng and Jiande were identified as predominantly SEO and HTN, respectively, and those from individuals in Shanghai had an indeterminant serotype defined by these two techniques. The HI test appears to be a simple and reliable way of determining the predominant hantavirus that causes HFRS in a given geographic area.


Clinical and hematological characteristics of 300 COVID-19 patients in Erbil, Kurdistan Region, Iraq.
COVID-19 primarily presents as a respiratory tract infection, but studies indicate that it could be considered a systemic disease that can spread to affect multiple organ systems, including respiratory, cardiovascular, gastrointestinal, hematopoietic, neurological, and immune systems. To describe and analyze the clinical and hematological characteristics of 300 hospitalized COVID-19 patients in Erbil, Kurdistan. This retrospective study included 300 patients of any age admitted to hospital due to confirmed COVID-19 between September 2020 and February 2021. Cases were diagnosed by reverse transcriptase polymerase chain reaction assays of nasopharyngeal swab specimens. The highest proportion of patients were aged 21-40 years. The most common symptoms among the patients were myalgia (66.7%), fatigue (62.3%), headache (50.7%), and chest pain (52.7%). Differences in hematological and biochemical parameters were observed between deceased and recovered patients. Only the mid-range absolute count percentage (MID%) was significantly higher in the recovered patients than in the deceased ones (6.41% vs. 4.48, p = 0.019). Death was significantly higher among older patients (>40 years) than younger ones (≤40 years) (6.8% vs. 1.3%, p = 0.015), diabetic than non-diabetic (10.8% vs. 3%, p = 0.047), and those having chronic diseases than those without chronic diseases (10.6% vs. 2.1%, p = 0.006). Different hematological and biochemical parameter findings were observed among the COVID-19 patients. Low MID%, older age, and presence of diabetes mellitus and chronic disease were significantly associated with death among COVID-19 patients.


Half-life of the duck hepatitis B virus covalently closed circular DNA pool in vivo following inhibition of viral replication.
Covalently closed circular DNA (cccDNA) is a crucial intermediate in the replication of hepadnaviruses. We inhibited the replication of duck hepatitis B virus in congenitally infected ducks with a combination of lamivudine and a dideoxyguanosine prodrug. Inhibition of viral replication should prevent renewal of the cccDNA pool, and its decay was measured in liver biopsy samples collected over a 5-month period. In three ducks, the cccDNA pools declined exponentially, with half-lives ranging from 35 to 57 days. In two others, the pools declined exponentially for about 70 days but then stabilized at about 6 copies/diploid genome. The selection of drug-resistant virus mutants is an unlikely explanation for this unexpected stabilization of cccDNA levels. Liver sections stained for the cell division marker PCNA showed that animals in which cccDNA loss was continuous had significantly greater numbers of PCNA-positive nuclei than did those animals in which cccDNA levels had plateaued.


The use of 'normal' and 'transformed' gynandromorphs in mapping the primordial germ cells and the gonadal mesoderm in Drosophila.
The primordial germ cells and the gonadal mesoderm were mapped in the Drosophila embryo by analyzing the patterns of mosaicism in 'normal' and 'transformed' gynandromorphs. Relative to the adult cuticular markers the germ cells map as the posterior most structure, which coincides with their known location in the blastoderm embryo. These data support the hypothesis that the gynandromorph map reflects the real position of the primordia in the embryo. Since after the blastoderm stage the primordial germ cells migrate anteriorly these data also indicate that the map in fact corresponds to the blastoderm stage and not to a later stage of development. The genital disc maps at a single median primordium anterior and ventral to the germ cells, the gonadal mesoderm is located anterior to the genital disc and also forms a single median primordium on the ventral side of the embryo. The primordia for the genital disc and the gonadal mesoderm are unusually large in size, which presumably reflects some indeterminacy of the cell lineage leading to an 'expansion' of the map.


Continuation rates of long-acting methods of contraception. A comparative study of Norplant implants and intrauterine devices.
Following adverse widespread publicity in the United Kingdom and the United States, it is commonly believed that discontinuation rates for the contraceptive implants Norplant in the UK are high. We have compared discontinuation rates between new intrauterine device (IUD) users (253 women) and new Norplant implant users (502 women) over 33 months following the introduction of Norplant implants among a population of women attending the same clinic and counseled in the same manner by the same group of providers. Women choosing the IUD were slightly older and were more likely to be changing their contraceptive method because of dissatisfaction with their current method. Nor plant implant users were more likely to have completed their families. Continuation rates for Norplant implants were significantly higher than for IUD at 12, 18, and 24 months after insertion. At 24 months, continuation rates for Norplant implants were 72% compared with rates of 55% for IUD users. Higher continuation rates may be related more to factors associated with the providers than with the users of these two long-acting methods.


Repression of acetyl-coenzyme A carboxylase by unsaturated fatty acids: relationship to coenzyme repression.
It has been reported that the level of d-biotin in the growth medium of Lactobacillus plantarum regulates the synthesis of apoacetyl-coenzyme A (CoA) carboxylase; high levels cause repression, and deficient levels effect derepression. In this study, evidence has been obtained which suggests that coenzyme repression by biotin is an indirect effect; i.e., biotin regulates the synthesis of unsaturated fatty acids which are the true repressors of the acetyl-CoA carboxylase. This was observed in an experiment in which long-chain unsaturated fatty acids were added to media containing deficient, sufficient, or excess levels of d-biotin. In every case, independently of the biotin concentration for growth, the unsaturated fatty acids caused a severe repression of the carboxylase. Saturated fatty acids were without effect. The level of oleic acid required to give maximal repression was 50 mug/ml. The free fatty acids had no adverse effect on the activity of the cell-free extracts nor on the permeation of d-biotin into the cell. Saturated and unsaturated fatty acids decreased the rate of holocarboxylase formation from d-biotin and the apoacetyl-CoA carboxylase in the extracts. It is concluded that there are at least three mechanisms that control the acetyl-CoA carboxylase in this organism: (i) indirect coenzyme repression by d-biotin, (ii) repression by unsaturated fatty acids, and (iii) regulation of the activity of the holocarboxylase synthetase by both saturated and unsaturated fatty acids.


Oral desensitization to penicillin in necrotizing (malignant) external otitis.
Penicillin allergy can complicate the treatment of life-threatening infections. When a beta-lactam (penicillin) drug is the treatment of choice, true allergy can be safely overcome by a recent, oral method of desensitization to penicillin. Patients with positive skin test results can be desensitized within four hours with oral, subcutaneous, and then intramuscular administration of progressively increased doses of penicillin G. We used this method successfully in a patient with severe necrotizing (malignant) external otitis.


Increasing hip fractures in patients receiving hemodialysis and peritoneal dialysis.
Dialysis patients are at increased risk for hip fractures. Because changes in treatment of metabolic bone disease in this population may have impacted bone fragility, this study aims to analyze the longitudinal risk for fractures in hemodialysis (HD) and peritoneal dialysis (PD) patients. Using the United States Renal Data System database from 1992 to 2009, the temporal trend in hip fractures requiring hospitalization was analyzed using an overdispersed Poisson regression model. Generalized Estimating Equations were used to assess the adjusted effect of dialysis modality on hip fractures. 842,028 HD and 87,086 PD patients were included. There was a significant temporal increase in hip fractures in both HD and PD with stabilization of rates after 2005. With stratification, the increase in fractures occurred in patients who were white and over 65 years of age. In adjusted analyses, HD patients had 1.6 times greater odds of hip fracture than PD patients (OR 1.60 95% CI 1.52, 1.68, p < 0.001). In contrast to the declining hip fracture rates in the general population, we identified a temporal rise in incidence of hip fractures in HD and PD patients. HD patients were at a higher risk for hip fractures than PD patients after adjustment for recognized bone fragility risk factors. The increase in fracture rate over time was limited to older white patients in both HD and PD, the demographics being consistent with osteoporosis risk. Further research is indicated to better understand the longitudinal trend in hip fractures and the discordance between HD and PD.


Effects of Combined High Hydrostatic Pressure and Dense Phase Carbon Dioxide on the Activity, Structure and Size of Polyphenoloxidase.
High hydrostatic pressure (HHP) may activate undesirable enzymes such as polyphenoloxidase (PPO). Carbon dioxide (CO2 ) addition to HHP could increase enzyme inactivation. We investigated the inactivation of combined HHP and dense phase carbon dioxide process on activity, secondary conformation and size of pure PPO from mushroom. Solutions (2.35μM, in phosphate buffer pH 6.8) were treated with HHP alone (HHP), or 3.6% w/w of CO2 was injected into the package (HHP+CO2). Treatment conditions were 600 MPa, 20 °C, for 1, 3, 5, 7, and 9 min. HHP+CO2 treatment significantly decreased residual enzyme activity (REA) to 30% to 12% after 1 to 9 min, respectively, whereas only HHP had no significant effect. Both HHP and HHP+CO2 treatments caused changes in secondary conformations, however HHP+CO2 changes were more extensive. Alpha-helix fractions were reduced by 32% and 41%, while β sheet, turn and unordered increased by 63% and 213%, 100% and 71%, and 118% and 82% for HHP and HHP+CO2, respectively after 9 min. The protein size in HHP+CO2 samples was 5- to 6-fold larger than that of Control and HHP treatment, and this increase was inversely correlated with REA. The best inactivation kinetics of HHP+CO2 model was the 2-fractional model with 2 simultaneous 1st-order steps, contributing 70% and 30% to original enzyme activity, with k(labile) = 12.15 min(-1) and k(stable) = 0.07 min(-1), respectively. No recovery in activity, secondary conformation and size in all samples were observed after 1-mo storage. Addition of CO2 in HHP treatment can improve enzyme inactivation, and therefore product shelf-life and quality. High hydrostatic pressure (HHP) achieves the safety of foods as a nonthermal method, but it may activate undesirable enzymes resulting in short shelf life due to, for example flavor and color changes. Our study determined that addition of CO2 to HHP has significant effects on enzyme inactivation, secondary conformational and molecular size changes of mushroom PPO. No recovery in activity, secondary conformation and size in all samples were observed after 1 mo storage at 4 °C. This combined process increases product shelf life, in addition to safety and nutrient preservation.


Forecasting Health Indicators Of Pakistan.
Forecasting of health indicators is of great importance for health policy makers. This study is aimed to forecast some important health indicators like crude death rate (CDR), crude birth rate (CBR), and infant mortality rate (IMR) and total fertility rate (TFR) of Pakistan. In this retrolective study, annual data of these indicators for years 1984-2010 have been used. The simple linear regression model with time as independent variable has been used to forecast these health indicators. The within-sample forecast results are close enough to the actual values. All the forecast values of the stated indicators tend to decrease with time. The forecast values of CDR, CBR, IMR and TFR for year 2020 are 12.85, 5.61, 43.61 and 0.93, respectively. Although the forecast values show an improvement in health indicators of Pakistan but the IMR is expected to remain high even in 2020, a concern for the health policy makers.


Paper and paperboard industry protocol for sampling and analysis of recycled materials intended for food packaging applications.
This paper describes the Recycled Paperboard Technical Association (RPTA) Sampling and Analysis Protocol that RPTA member mills can use to determine that paperboard produced from recycled fibre may safely be used in food contact applications. Application of this Protocol helps to ensure compliance with the US Food and Drug Administration (FDA) regulations outlined in 21 CFR 176.260. Health risk-based allowable concentrations for potential unintended chemical constituents in the paperboard have been calculated. The protocol provides a methodology for mills to determine the concentrations of these chemicals in their paperboard for comparison with the allowable concentrations. This methodology includes guidance on what to test for, frequency of testing, sample collection methods, analytical methods and interpretation of testing results. This paper explains how and why the RPTA Protocol was developed, how it is used today, what changes have been made through the first half of 2004 and what changes may be expected in the future.


JNKs function as CDK4-activating kinases by phosphorylating CDK4 and p21.
Cyclin D-CDK4/6 are the first cyclin-dependent kinase (CDK) complexes to be activated by mitogenic/oncogenic pathways. They have a central role in the cell multiplication decision and in its deregulation in cancer cells. We identified T172 phosphorylation of CDK4 rather than cyclin D accumulation as the distinctly regulated step determining CDK4 activation. This finding challenges the view that the only identified metazoan CDK-activating kinase, cyclin H-CDK7-Mat1 (CAK), which is constitutively active, is responsible for the activating phosphorylation of all cell cycle CDKs. We previously showed that T172 phosphorylation of CDK4 is conditioned by an adjacent proline (P173), which is not present in CDK6 and CDK1/2. Although CDK7 activity was recently shown to be required for CDK4 activation, we proposed that proline-directed kinases might specifically initiate the activation of CDK4. Here, we report that JNKs, but not ERK1/2 or CAK, can be direct CDK4-activating kinases for cyclin D-CDK4 complexes that are inactivated by p21-mediated stabilization. JNKs and ERK1/2 also phosphorylated p21 at S130 and T57, which might facilitate CDK7-dependent activation of p21-bound CDK4, however, mutation of these sites did not impair the phosphorylation of CDK4 by JNKs. In two selected tumor cells, two different JNK inhibitors inhibited the phosphorylation and activation of cyclin D1-CDK4-p21 but not the activation of cyclin D3-CDK4 that is mainly associated to p27. Specific inhibition by chemical genetics in MEFs confirmed the involvement of JNK2 in cyclin D1-CDK4 activation. Therefore, JNKs could be activating kinases for cyclin D1-CDK4 bound to p21, by independently phosphorylating both CDK4 and p21.


Escherichia coli Chromosome Copy Number Measurement Using Flow Cytometry Analysis.
Flow cytometry is a high-throughput technique that analyzes individual particles as they pass through a laser beam. These particles can be individual cells and by detecting cell-scattered light their number and relative size can be measured as they pass through the beam. Labeling of molecules, usually via a fluorescent reporter, allows the amount of these molecules per cell to be quantified. DNA content can be estimated using this approach and here we describe how flow cytometry can be used to assess the DNA content of Escherichia coli cells.


How does supercoiling regulation on a battery of RNA polymerases impact on bacterial transcription bursting?
Transcription plays an essential role in gene expression. The transcription bursting in bacteria has been suggested to be regulated by positive supercoiling accumulation in front of a transcribing RNA polymerase (RNAP) together with gyrase binding on DNA to release the supercoiling. In this work, we study the supercoiling regulation in the case of a battery of RNAPs working together on DNA by constructing a multi-state quantitative model, which allows gradual and stepwise supercoiling accumulation and release in the RNAP transcription. We solved for transcription characteristics under the multi-state bursting model for a single RNAP transcription, and then simulated for a battery of RNAPs on DNA with T7 and Escherichia coli RNAP types of traffic, respectively, probing both the average and fluctuation impacts of the supercoiling regulation. Our studies show that due to the supercoiling accumulation and release, the number of RNAP molecules loaded onto the DNA vary significantly along time in the traffic condition. Though multiple RNAPs in transcription promote the mRNA production, they also enhance the supercoiling accumulation to suppress the production. In particular, the fluctuations of the mRNA transcripts become highly pronounced for a battery of RNAPs transcribing together under the supercoiling regulation, especially for a long process of transcription elongation. In such an elongation process, though a single RNAP can work at a high duty ratio, multiple RNAPs are hardly able to do so. Our multi-state model thus provides a systematical characterization of the quantitative features of the bacterial transcription bursting; it also supports improved physical examinations on top of this general modeling framework.


CHARACTERIZATION AND EXPERIMENTAL MEASUREMENTS OF SCATTER DOSE AT CARDIOLOGIST'S EYES DURING PAEDIATRIC INTERVENTIONAL CARDIOLOGY PROCEDURES IN COSTA RICA.
This paper presents the results of the first characterization and experimental measurements of scatter dose at cardiologist's eyes for the only X-ray system that performs all paediatric Interventional cardiology procedures in Costa Rica. Entrance surface air kerma (ESAK) and the scatter dose values were measured on phantoms of 4-20 cm thicknesses of polymethyl methacrylate slabs. Image quality was evaluated using DICOM images of a test object Leeds TOR 18-FG, through the numerical parameters signal-to-noise ratio (SNR), high-contrast spatial resolution (HCSR) and figure of merit (FOM). When PMMA thickness is increased and during a move from low fluoroscopy to cine modes, ESAK, SNR, HCSR and FOM values range from 0.44 to 391.0 μGy fr-1; 2.8 to 14.89; 3.17 to 15.54 and 0.51 to 79.94, respectively. The highest scattered dose rates recorded during the simulations were 1.79 and 8.04 mSv h-1 for the high fluoroscopy and cine modes, respectively.


MACOP-B treatment for intermediate and high-grade non-Hodgkin's lymphomas at diagnosis and in relapse.
Between October, 1984 and October, 1987 a study program was carried out to evaluate the efficacy of MACOP-B in the advanced stages of intermediate/high-grade malignancy non-Hodgkin's lymphomas (NHL). Thirty patients were treated at diagnosis: 14 with D-E-F histology (median age = 56.5 years) and 16 with G-H histology (median age = 46.5). Complete remission (CR) rate was 42.8% for the D-E-F subgroup and 81.2% for the G-H subgroup. Bone marrow involvement was the major adverse factor for CR achievement in patients with intermediate-grade NHL. Overall, disease stage, bulky presentation and the presence of systemic symptoms did not significantly affect response to therapy. Survival curves predict 73% of patients alive at 45 months (median follow-up = 30 mo.). No significant differences were seen between D-E-F (64%; median follow-up = 36 mo.) and the G-H patients (81%; median follow-up = 27 mo.). The disease-free survival curve for all patients in CR reached a plateau phase at 78% (median follow-up = 30 mo). MACOP-B was much less effective when employed in 10 patients at relapse; only 2 out of these 10 reached a durable CR, which persisted 51 and 27 mo. after MACOP-B. The remaining 8 patients had a partial response, followed closely by disease progression: 7 died, whereas 1 patient is still alive after salvage therapy with bone marrow transplant. Thus, MACOP-B proved to be effective in patients at diagnosis with G-H histology.(ABSTRACT TRUNCATED AT 250 WORDS)


Vicinal dihalonium ions: diprotonated and dimethylated chlorine [H2Cl2(2+), (CH3)2Cl2(2+)] and bromine [H2Br2(2+), (CH3)2Br2(2+)] dications.
High level ab initio calculations at the MP2/cc-pVTZ, CCSD(T)/cc-pVTZ, and CASSCF(6,6)/cc-pVTZ levels were performed to investigate geometries and energies of superelectrophilic diprotonated, and dimethylated molecular chlorine (Cl2) and bromine (Br2) dications. Diprotonated chlorine and diprotonated bromine dications 3a and 6a, respectively, were found to be lowest energy minima. The isomeric dications, 3b and 6b, are also minima on the potential energy surfaces but they are significantly less stable than the structures 3a and 6a by 33.6 and 30.9 kcal/mol, respectively. On the basis of computed G2 energies, proton affinities and related thermodynamic parameters were also calculated. Dications 3a and 6a have substantial kinetic barriers for deprotonation. Their homolytic dissociation are however facile. Dimethylated molecular chlorine and bromine dications 3g and 6g, respectively, were also found to be global energy minima. These vicinal dihalonium or the corresponding protosolvated species are expected to form either in the superacidic media or in the gas phase.


Trends in Hospitalization and Inpatient Outcomes of Behçet's Disease: A Nationwide Inpatient Sample Study.
Objective After an extensive review of the literature, we discovered that no study had addressed trends in hospitalization for people with Behçet's disease (BD). Hence, in this study, we explore multiple variables in patients with BD in the US for the year 2016. Methods We analyzed the data relating to hospitalized patients for the year 2016 using the National Inpatient Sample (NIS) database with a listed discharge diagnosis of BD based on the International Classification of Diseases, 10th Revision (ICD-10) diagnosis code M35.2. The mean age in years, alive discharges, lumbar puncture procedures, type of hospital, the Charlson Comorbidity Index (CCI), comorbidities, mean length of stay (LOS) and factors affecting it, and total cost and charges for the admissions were analyzed. A p-value of <.05 was considered statistically significant. Results A total of 2,605 discharges with the diagnoses of BD were identified among 35.7 million overall discharges in 2016. Among patients hospitalized with underlying BD, the majority were white and female. The mean hospital LOS was 5.57 ± 0.37 days, which is higher than in the general population and statistically significant (5.57 days vs 4.62 days; p: 0.009). Mean LOS in patients undergoing lumbar puncture was 8.54 ± 2.91 days. Patients with BD had lower medical comorbidity burden (16.9% with a CCI of ≥3) vs the general population (24.67% with a CCI of ≥3) (p: 0.00). Medical comorbidities with a statistically significant difference in their prevalence in the two groups were renal disease, dementia, peptic ulcer disease, heart failure, rheumatologic disorders, malignancy, and dyslipidemia. Conclusion Increased awareness about this rare condition in an inpatient setting will help in the early identification of the disease and associated complications. This will help caregivers to provide quality care in a timely manner, thereby decreasing the morbidity, mortality, LOS, and hospital costs associated with BD.


[Efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia].
To observe the clinical efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia. Fifty patients with asthenospermia and teratospermia meeting the inclusion criteria were randomly divided into a blank control (n = 10) and a medication group (n = 40), the former provided with fertility guidance and the latter treated with Jujing Decoction combined with lipoic acid. After 12 weeks of treatment, the clinical therapeutic effects were evaluated by comparing the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically abnormal sperm (MAS), rate of acrosome integrity, sperm DNA fragment index (DFI) and pregnancy rate between the two groups. Compared with the control group, the medication group achieved a significantly higher overall effectiveness rate (10% [1/10] vs 88.89% [32/36], P < 0.05) and pregnancy rate (0% [0/10] vs 8.33% [3/36], P < 0.05) after treatment. The medication group also showed remarkably increased PMS from (21.04 ± 6.49)% to (32.66 ± 7.05)%, decreased MAS from (98.31 ± 1.28)% to (96.52 ± 1.11)%, elevated acrosome integrity from (42.18 ± 16.67)% to (60.42 ± 11.61)%, and reduced sperm DFI from (21.92 ± 6.96)% to (12.37 ± 3.79)%, all with statistically significant differences compared with the blank control group. Jujing Decoction combined with lipoic acid can significantly improve sperm motility, reduce MAS and DFI and increase the pregnancy rate through antioxidant stress, and has a high clinical safety.


Ciprofloxacin-induced Hepatotoxicity in a Healthy Young Adult.
Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that is widely used in the treatment of many common infections, including urinary tract infections (UTIs). Despite the increase in Escherichia coli resistance to ciprofloxacin, especially in the United States (US), clinicians continue to utilize the high bioavailability of this drug in urine to counter UTIs. A rare adverse effect following use of ciprofloxacin is drug-induced hepatitis. In this case report, we describe a young 29-year-old female with a previous medical history significant for pyelonephritis and ovarian cyst who presented to the emergency room with signs and symptoms suggestive of progressive liver injury for two weeks that started two days after a complete course of ciprofloxacin therapy for a UTI. An extensive workup failed to identify a particular cause for the hepatotoxicity. The associated onset of symptoms following ciprofloxacin use, the pattern of hepatic enzyme elevation coupled with abdominal pain suggestive of liver pathology, and the resolution of all symptoms following supportive therapy all pointed towards the possible diagnosis of ciprofloxacin-induced hepatotoxicity. The patient was treated with supportive therapy, and subsequently, her symptoms resolved over the next few days with the improvement of her liver enzyme levels. The patient was discharged with instructions to avoid ciprofloxacin and other fluoroquinolones in the future. Clinicians should maintain a high degree of suspicion when treating patients with ciprofloxacin who subsequently develop signs and/or symptoms of liver injury.


gamma-H2AX in bystander cells: not just a radiation-triggered event, a cellular response to stress mediated by intercellular communication.
The recent years have witnessed a rapid accumulation of experimental data showing that ionizing radiation elicits a plethora of biological effects in unirradiated cells receiving bystander signals from hit cells. This so-called radiation-induced bystander effect (RIBE) manifests in various ways including changes in gene expression, genetic and epigenetic alterations, as well as increases in cell transformation and cell death. Our group and others found that DNA double-stranded breaks (DSBs), directly measured by the gamma-H2AX focus formation assay, accumulate in bystander cells in a number of experimental systems such as human cultured cells, human three-dimensional tissue models and in mice. In addition, we recently found that various other sources of cell stress, including media from cancerous cells resulted in a DNA damage response (DDR) in normal human cells that is reminiscent of RIBE. These results suggest that the RIBE may be part of a more general stress response, however, the molecular mechanism underpinning the formation of DNA DSBs in bystander cells is still unclear. This extra view points to some possibilities that might explain why DDR in human cells can be observed under bystander conditions.


Proteomic and metabolomic strategies to investigate HIV-associated neurocognitive disorders.
Diagnosing neurodegenerative diseases, monitoring their progression and assessing responses to treatments will all be aided by the identification of molecular markers of different stages of pathology. Protein biomarkers for HIV-associated neurocognitive disorders that have been discovered using proteomics include complement C3, soluble superoxide dismutase and a prostaglandin synthase. Metabolomics has not yet been widely used for biomarker discovery, but early work shows that it has great potential.


Numerical taxonomy of some bacteria isolated from antarctic and tropical seawaters.
Pfister, Robert M. (Lamont Geological Observatory, Palisades, N.Y.), and Paul R. Burkholder. Numerical taxonomy of some bacteria isolated from Antarctic and tropical seawaters. J. Bacteriol. 90:863-872. 1965.-Microorganisms from Antarctic seas and from tropical waters near Puerto Rico were examined with a series of morphological, physiological, and biochemical tests. The results of these analyses were coded on punch cards, and similarity matrices were computed with a program for an IBM 1620 computer. When the matrix was reordered by use of the single-linkage technique, and the results were plotted with four symbols for different per cent similarity ranges, nine groups of microorganisms were revealed. The data suggest that organisms occurring in different areas of the open ocean may be profitably studied with standardized computer techniques.


Decellularization of Human Internal Mammary Artery: Biomechanical Properties and Histopathological Evaluation.
This study undertook to create small-diameter vascular grafts and assess their structure and mechanical properties to withstand arterial implantation. Twenty samples of intact human internal mammary arteries (IMAs) were collected and decellularized using detergent-based methods. To evaluate residual cellular and extracellular matrix (ECM) components, histological analysis was performed. Moreover, collagen typing and ECM structure were analyzed by Picrosirius red and Movat's pentachrome staining. Scanning electron microscopy was also applied to assess microarchitecture of both endothelial and adventitial surfaces of native and decellularized arterial samples. Furthermore, mechanical tests were performed to evaluate the rigidity and suture strength of the arteries. Human IMAs were completely decellularized in all three segments (proximal, middle, and distal). ECM proteins such as collagen and elastic fibers were efficiently preserved and no structural distortion in intima, media, and adventitial surfaces was observed. The parameters of the mechanical tests revealed no significant differences in the mechanical properties of decellularized arteries in comparison to native arteries with considerable strength, suture retention, and stress relaxation (Young's modulus [MPa] = 0.22 ± 0.023 [native] and 0.22 ± 0.015 [acellular]; and suture strength 0.56 ± 0.19 [native] vs. 0.56 ± 0.12 [acellular], respectively). Decellularized IMA represents a potential arterial scaffold as an alternative to autologous grafts for future arterial bypass surgeries. By this technique, microarchitecture and mechanical integrity of decellularized arteries were considerably similar to native arteries. The goal of this study was to introduce an efficient method for complete decellularization of human IMA and evaluate the ECM and biomechanical properties.


TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling.
Colorectal cancer (CRC) has become a major public health problem, ranking as the third most common type of cancer. Our previous study has revealed that TCF21 is frequently silenced by promoter hypermethylation in both CRC cell lines and primary CRC, with TCF21 methylation being significantly correlated with lymph node invasion. In this study, we further analyze the expression of TCF21 in CRC tissues and investigate the role of TCF21 in CRC in vitro and in vivo. We also explore the possible pathway regulated by TCF21. We thus demonstrate that decreased levels of TCF21 are associated with the pathological stage, clinical stage and lymph node metastasis, indicating a poor prognosis in CRC patients; overexpression of TCF21 inhibits cell proliferation, migration and invasion in the colorectal cell lines HCT116 and HT29. Furthermore, TCF21 functions as a tumor suppressor probably through inactivation of PI3K/AKT signaling and inhibition of MMPs. Our results suggest that enhancement of TCF21 levels may be a potential strategy to facilitate the prevention and treatment of CRC in the clinic.


[Genetic control of the stress response of the system of juvenile hormone metabolism in Drosophila virilis].
Metabolism of juvenile hormone (JH) in 11-day-old D. virilis flies from resistant and sensitive lines and in hybrids of these lines was analyzed after short-term heat stress (4 h, 38 degrees C). The level of JH hydrolysis after stress remained constant in the sensitive line, but drastically decreased in the resistant one. Between-line differences of the metabolic JH response to stress were shown to be controlled monogenically or by a block of closely linked genes. The allele of the resistant line was dominant.


Limited Proteolysis of Cyclooxygenase-2 Enhances Cell Proliferation.
Accumulating evidence suggests that the cyclooxygenase-2 (COX-2) enzyme has additional catalytic-independent functions. Here we show that COX-2 appears to be cleaved in mouse and human tumors, which led us to hypothesize that COX-2 proteolysis may play a role in cell proliferation. The data presented herein show that a K598R point mutation at the carboxyl-terminus of COX-2 causes the appearance of several COX-2 immunoreactive fragments in nuclear compartments, and significantly enhances cell proliferation. In contrast, insertion of additional mutations at the border of the membrane-binding and catalytic domains of K598R COX-2 blocks fragment formation and prevents the increase in proliferation. Transcriptomic analyses show that K598R COX-2 significantly affects the expression of genes involved in RNA metabolism, and subsequent proteomics suggest that it is associated with proteins that regulate mRNA processing. We observe a similar increase in proliferation by expressing just that catalytic domain of COX-2 (ΔNT- COX-2), which is completely devoid of catalytic activity in the absence of its other domains. Moreover, we show that the ΔNT- COX-2 protein also interacts in the nucleus with β-catenin, a central regulator of gene transcription. Together these data suggest that the cleavage products of COX-2 can affect cell proliferation by mechanisms that are independent of prostaglandin synthesis.


A functional antibody lacking N-linked glycans is efficiently folded, assembled and secreted by tobacco mesophyll protoplasts.
A potential drawback in the use of plants as an expression platform for pharmaceutical proteins such as antibodies is that plant-specific N-glycosylation can result in proteins with altered function and potential antigenicity. In many cases, the N-glycans are essential for the correct folding, assembly and transport of the recombinant proteins. We tested whether progressive removal of glycosylation sites had a detrimental effect on the synthesis, assembly and secretion of a plant-made immunoglobulin G, Guy's 13. Our results indicate that the plant secretory pathway can cope well with aglycosylated antibody chains. The immunoglobulin without N-linked glycans is correctly assembled and secreted by tobacco protoplasts. Capture enzyme-linked immunosorbent assay also shows that antigen-binding properties are unaffected. Our results therefore suggest one possible alternative to the engineering of a humanized glycosylation machinery in plants.


Purkinje cells pathology in schizophrenia. A morphometric approach.
Schizophrenia is a brain disorder that affects more than 21 million people worldwide. Ventricle enlargement and reduction in the volume of the temporal lobe overall and in medial temporal structures constitutes the main macroscopic findings, whilst synaptic and spinal changes as well as gliosis in the hippocampal formation, the prefrontal and the entorhinal cortex stand among cardinal microscopic findings in the schizophrenic brains. In recent years, accumulated evidence comes to light about the role of cerebellum in the pathophysiology of schizophrenia. The present study is based on the morphological analysis and 3D neuronal reconstruction of the Purkinje cells from 10 schizophrenic brains and 10 normal controls. Significant morphological alterations such as loss of distal and terminal dendritic branches and decrease of the density of the dendritic spines constitute the main morphological findings found in the present study. The present findings may be added to accumulated evidence on macroscopic and microscopic pathology of the cerebellum in schizophrenia. Morphological alterations of Purkinje cells seem to be a central feature of neuropathology of schizophrenia, reflecting to impairment of neuronal connectivity and functionality, and related to motor and cognitive symptoms.


Long-term working memory deficits after concussion: electrophysiological evidence.
Persistent complaints of lingering memory and concentration difficulties are common following a concussion, although the brain basis of these is unknown. Some suggest abnormalities can be found on the P300 event-related potential component, recorded using electroencephalography (EEG), despite unobservable cognitive impairments. To examine the P300 and cognitive performance following a remote concussion during an n-back task that varies in working memory load. Seventeen participants with a remote concussion and 17 controls performed a visual n-back task in which working memory demands were systematically increased by manipulating cognitive load. Participants also completed neuropsychological and self-report measures. The concussion group showed a decrease in P300 amplitude compared to controls that was independent of working memory load on the n-back task. While no performance differences were observed between groups, P300 amplitude was negatively correlated with response times at higher loads in both groups. High functioning young adults with a remote concussion may have inefficient recruitment of processing resources for target identification, evident by the attenuated P300. The negative correlations between response time and P300 amplitude suggest that the time necessary to accurately respond to targets increases as the efficiency of allocating processing resources decreases during highly demanding working memory tasks.


Retrieval of patients with hepatitis C who were lost to follow-up in Southern Denmark.
The goal of the C-Free-South project is to eliminate hepatitis C (HCV) in the Region of Southern Denmark (1.2 million inhabitants). One target group consists of people with HCV who had received care but were lost to follow-up. The study aim was to evaluate program efficacy in locating these patients and getting them into care. Patients were contacted if they were HCV-RNA positive and age 18+ years, registered in the clinical hepatitis database as of November 1, 2019, and had no scheduled HCV-related appointment. They were contacted at 2-month intervals by phone or letter. For patients who did not respond, we asked their general practitioner to refer them, if possible. We identified 69 (7%) patients in the database who were listed as untreated and not being followed up. We successfully contacted 54 (78%), and the remaining 15 (22%) did not respond to our contacts. To date, 45 (65%) had initiated treatment, one (1%) had rejected treatment, and eight (12%) did not show up to their appointments. Among those receiving treatment, 20 (44%) responded after the first contact, 18 (40%) after the second contact, and 7 (16%) after informing the general practitioner. An intensified and persistent effort made it possible to reach most HCV patients lost to follow-up. All new contact attempts increased the possibility that patients would receive treatment. Nevertheless, 22% of HCV patients lost to follow-up did not respond to repeated contact attempts.


Bone microstructural defects and osteopenia in hemizygous βIVSII-654 knockin thalassemic mice: sex-dependent changes in bone density and osteoclast function.
β-Thalassemia, a hereditary anemic disorder, is often associated with skeletal complications that can be found in both males and females. The present study aimed to investigate the age- and sex-dependent changes in bone mineral density (BMD) and trabecular microstructure in β(IVSII-654) knockin thalassemic mice. Dual-energy X-ray absorptiometry and computer-assisted bone histomorphometry were employed to investigate temporal changes in BMD and histomorphometric parameters in male and female mice of a β(IVSII-654) knockin mouse model of human β-thalassemia, in which impaired splicing of β-globin transcript was caused by hemizygous C→T mutation at nucleotide 654 of intron 2. Young, growing β(IVSII-654) mice (1 mo old) manifested shorter bone length and lower BMD than their wild-type littermates, indicating possible growth retardation and osteopenia, the latter of which persisted until 8 mo of age (adult mice). Interestingly, two-way analysis of variance suggested an interaction between sex and β(IVSII-654) genotype, i.e., more severe osteopenia in adult female mice. Bone histomorphometry further suggested that low trabecular bone volume in male β(IVSII-654) mice, particularly during a growing period (1-2 mo), was primarily due to suppression of bone formation, whereas both a low bone formation rate and a marked increase in osteoclast surface were observed in female β(IVSII-654) mice. In conclusion, osteopenia and trabecular microstructural defects were present in both male and female β(IVSII-654) knockin thalassemic mice, but the severity, disease progression, and cellular mechanism differed between the sexes.


Esophageal chemical clearance and mucosa integrity values in refractory gastroesophageal reflux disease patients with different esophageal dynamics.
Esophageal post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI), novel impedance-based markers of reflux burden, are associated with esophageal dynamics. We aim to investigate the characteristics of PSPWI and MNBI in Chinese refractory gastroesophageal reflux disease (RGERD) patients with different esophageal dynamic changes. 201 RGERD and 76 functional heartburn patients, undergone off-PPI endoscopy, esophageal manometry and impedance-pH monitoring, were included. Comparisons of conventional and novel impedance-pH metrics were made among different esophageal dynamics groups. Receiver operating-characteristic analyses were utilized to evaluate the diagnostic efficacy of PSPWI and MNBI in differentiating abnormal esophageal dynamics. Correlations were used to investigate their associated factors. PSPWI and MNBI of RGERD with esophagogastric junction (EGJ) injury and esophageal dysmotility were lower than EGJ injury alone or normal dynamics (p < 0.05 for both comparisons). PSPWI with esophageal peristalsis abnormality was lower than EGJ injury (p = 0.049), while MNBI showed no statistical difference. PSPWI, MNBI and their combination have auxiliary diagnostic values for esophageal peristalsis [area under the curves (AUCs): 0.683, 0.656, 0.708)] while only their combination for EGJ injury (AUC: 0.610). And they positively correlated with esophageal motility while negatively correlated with ineffective swallows and acid reflux events. PSPWI and MNBI, indicating impairment of esophageal chemical clearance and mucosa integrity, were lower in RGERD patients with multiple esophageal dynamic injuries than single injuries or normal dynamics. Moreover, they provided useful contributing information for potential dynamic injuries if manometry has already been found normal or marginal.


Acute lymphocytic leukemia: role of hematopoietic stem cell transplantation in current management.
It is still unclear what the best postremission therapy is for young adults with acute lymphocytic leukemia (ALL). Encouraging results, supporting the superiority of allogeneic stem cell transplantation in CR1 compared with chemotherapy/ allogeneic stem cell transplantation (ASCT), are coming from the ongoing international prospective MRC UKALL XII /ECOG 2993 study. However, the transplant-related morbidity and mortality remain high. The detection of persistent minimal residual disease (MRD) after induction and consolidation therapy is being increasingly used to identify high-risk patients for whom allogeneic transplant may offer the only curative option. The ultimate aim is to determine whether the absence of MRD pretransplant can be used as a surrogate for low-risk adult ALL that can be cured without allogeneic transplantation.


[The use of pharmacological preparations for the study of calmodulin interaction with enzymes].
Calmodulin-dependent regulation of cyclic nucleotide phosphodiesterase and kinase phosphorylase activities as well as Ca2+-dependent regulation of kinase phosphorylase, mediated via the integrated calmodulin, were studied in presence of phenothiazine and butyrophenone series of pharmacological drugs. As compared with butyrophenones, phenothiazines were shown to be more effective inhibitors of calmodulin-dependent activation of the phosphodiesterase. Phenothiazines inhibited similarly the effect of calmodulin on activity of kinase phosphorylase, whereas they did not affect the Ca2+-dependent activity of kinase phosphorylase. At the same time, butyrophenones proved to inhibit the Ca2+-dependent activation of kinase phosphorylase, mediated via integrated calmodulin as well as these drugs inhibited uniformly the calmodulin-dependent regulation of both kinase phosphorylase and phosphodiesterase. The data obtained suggest that dissimilar effect of phenothiazines on calmodulin-dependent regulation of kinase phosphorylase and phosphodiesterase, carried out using dissimilar mechanisms, required an extreme caution in evaluation of physiological and biochemical experiments, where these drugs were used as means for study of calmodulin functions in biological processes.


Hysteroscopic evaluation of tubal peristaltic dysfunction in unexplained infertility.
It has been realised that rhythmic peristalsis of the ostia and tubes can be observed during hysteroscopy. The aim of this study was to examine the presence of tubal peristaltic dysfunction in unexplained infertility (UI). Hysteroscopy was performed in 35 women with UI and in 37 healthy fertile women. Bilateral tubal peristalses were assessed hysteroscopically by the observation of methylene blue injection and its transport to the Fallopian tubes. Tubal patency was evaluated with laparoscopic chromopertubation. Two women in control group (6.67%) and eight women in UI group (30.77%) had no tubal peristalsis, at least one tube with normal tubal patency. The difference was statistically significant (p = .019). Tubal peristaltic dysfunction may be a hidden cause of subfertility in women with bilateral patent Fallopian tubes. There is a definite need for larger trials to identify tubal peristaltic dysfunction as a cause of UI. Impact statement What is already known on this subject? Unexplained infertility has no identified pathophysiologic basis. It has been realised that rhythmic peristalsis of the ostia and tubes can be observed during hysteroscopy. What do the results of this study add? Tubal peristaltic dysfunction was detected in two tubes (3.70%) in a control group and nine tubes (19.57%) in women with unexplained infertility, when the tubes were patent. The difference was statistically significant (p = .012). What are the implications of these findings for clinical practice and/or further research? In cases of bilateral patent Fallopian tubes such as in unexplained infertility, tubal peristaltic dysfunction may be a hidden additional cause of subfertility.


Nursing students' knowledge about ventilator-associated pneumonia prevention guidelines: Effectiveness of a teaching program.
This study evaluated the effectiveness of an educational course that aimed to expand student nurses' knowledge about the guidelines for ventilator-associated pneumonia (VAP) prevention. In the pretest, the students revealed poor knowledge (mean score ± SD, 6.3 ± 2.8 out of 20). After completion of the educational program, participants in the experimental group showed a significant improvement (t105 = 14.9, P < .001). The control group showed no significant improvement. More focus on VAP prevention guidelines is essential in nursing curricula.


Subannular T-tubes for the treatment of adhesive otitis: how we do it.
Subannular T-tubes for the treatment of adhesive otitis: how we do it. Adhesive otitis is a chronic otitis media (OM) that consists of the adhesion of the tympanic membrane (TM) to the promontory. The aim of our study is to evaluate a new way of positioning subannular T-tubes (SATs) in patients affected by adhesive otitis. This study enrolled 22 patients (average age: 36.7 yo, 2.5 SD; M/F ratio: 14/8) affected by unilateral chronic adhesive otitis. All of the patients underwent the positioning of a SAT and a Silastic@ sheet in the tympanic cavity. The clinical course was evaluated, considering otoscopic and audiological variations. In our series, only one case of extrusion of tubes with residual perforation of TM was recorded. Auditory outcomes were satisfying in 18/22 patients (81.8%). The proposed addition of a Silastic disk seems to avoid a new adhesion of the tympanic membrane to the promontory and, therefore, prevents treatment failures. A longer follow-up and a larger case series are needed to prove the efficacy of this surgical variation. Finally, the positioning of SATs can be considered as a valid and safe procedure for the treatment of adhesive otitis.


Multifocal necrotizing fasciitis - case report.
Necrotizing fasciitis (NF) is a rare, life-threatening soft-tissue infection, characterized by rapidly spreading inflammation, with secondary necrosis of the fascia and surrounding tissues. It is mostly caused by group A beta-haemolytic streptococci or multibacterial. A case of the 25-year-old man admitted on September 2006 to the Department of Dermatology and Venereology with suspicion of erysipelas of the left upper limb and left foot is presented. On admission the pain, erythema, diffuse oedema of the left upper limb and erythema of the left foot were observed. Laboratory results revealed elevated: ESR, acute phase parameters (C-reactive protein, D-dimer), CPK and fibrinogen. Within 72-hours, despite treatment with antibiotics and anticoagulants, the oedema and pain increased, initial necrosis of the skin and extreme local tenderness appeared. Suspecting NF the patient had been transported to the Department of Surgery from where, after surgical debridement of devitalized tissue, was moved to the Intensive Care Unit and then transferred to the National Centre of Hyperbaric Medicine of the Medical University of Gdansk. Despite of repeated debridement, aggressive antibiotic therapy and hyperbaric oxygen therapy, necrosis was spreading. The patient developed sepsis and acute respiratory distress syndrome. Amputation of the left upper limb was performed. Five months later patient was admitted to ICU in Bialystok after a suicide attempt. After next four months he died. The dramatic course of the disease is the evidence, that having an adequate knowledge about early symptoms of NF can save patient's life.


Injuries associated with fractures of the transverse processes of the thoracic and lumbar vertebrae.
The records of 92 patients who sustained fractures of the transverse processes of thoracic or lumbar vertebrae between 1976 and mid-1982 were reviewed. The majority were injured in motor vehicle accidents. Trauma to abdominal viscera occurred in 19 patients including hepatic injuries in six, splenic injuries in 12, and colonic injuries in five. Hematuria was present in 51 patients and five of 51 had urinary tract injury requiring operative treatment. None of 34 patients without hematuria incurred anatomic disruption of the urinary tract. Thirty-two patients suffered other associated injuries, including thoracic, orthopedic, maxillofacial, and cerebral trauma. Fifteen patients incurred other spinal injuries. The overall mortality was 11% (ten patients). The mean Injury Severity Score in the 92 patients was 13.9. The frequency of abdominal visceral trauma with this bony injury (19/92-21%) suggests great energy expenditure and should alert physicians to seek other severe injuries.


Folate grafted Prussian Blue entrapped with gadolinium(III) as a new contrast agent for tumor-targeted magnetic resonant imaging.
A new generation of magnetic resonant imaging (MRI) contrast agents will simultaneously possess characteristics of high relaxivity, biotargeting ability and nontoxicity, referring that they are helpful to acquire better contrast imaging in the region of interest (e.g., tumors) without health risks. Colloidal Prussian blue with quasi-zeolite structure was introduced as a new type of nanosized scaffold to entrap Gd(III) ions via ion exchange and folate, one kind of cancer-targeting ligand, was intentionally grafted on its surface. The nanoparticulate contrast agent has T1 relaxivity of up to 23.9 mM(-1) s(-1). In vivo MRI illustrated a clear contrast enhancement specifically on the ovarian tumors transplanted on mice at a low dose. Furthermore, the contrast agent is stable and free of cytotoxicity. Therefore it might be a promising new MRI contrast agent for clinical applications.


[Pheochromocytoma--apropos a clinical case].
A case of a 43-year-old woman with severe sustained hypertension resistant to many antihypertensive drugs, frequent hypertensive crisis and symptoms suggestive of pheochromocytoma (symptomatic triad) is presented. Three of the four determinations of the urinary catecholamines metabolites have been normal as it was the only determination of plasmatic catecholamines. Abdominal sonography and CT scan detected a left adrenal mass, that have been histologically confirmed, after surgery, to be a pheochromocytoma. After adrenalectomy, the patient symptoms disappeared but she maintained mild hypertension easily controlled with drugs. The finding of normal plasmatic and urinary catecholamines values in a patient with sustained hypertension may suggest that we are handling with a case of essential hypertension and a superimposed pheochromocytoma with paroxysmal secretion. Some considerations are made essentially about specificity and sensitivity of diagnostic tests.


Nanoporous carbon supercapacitors in an ionic liquid: a computer simulation study.
Supercapacitors composed of carbon nanotube (CNT) micropores in the room-temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium tetrafluoroborate (EMI+BF4(-)) are studied via molecular dynamics (MD)computer simulations. It is found that the distribution of RTIL ions inside the micropore varies significantly with the pore size. Internal solvation of small (6,6) and (7,7) CNTs with an electrified interior wall is effected almost exclusively via counterions. Surprisingly, these counterions, even though they all have the same charge, lead to a charge density characterized by multiple layers with alternating signs. This intriguing feature is attributed to the extended nature of RTIL ion charge distributions, which result in charge separation through preferential orientation inside the electrified nanotubes. In the case of larger (10,10) and (15,15) CNTs, counterions and coions develop multilayer solvation structures. The specific capacitance normalized to the pore surface area is found to increase as the CNT diameter decreases from (15,15) to (7,7). As the pore size further reduces from (6,6) to(5,5), however, the specific capacitance diminishes rapidly. These findings are in excellent agreement with recent experiments with carbon-based materials. A theoretical model based on multiple charge layers is proposed to understand both the MD and experimental results.


Risk factors and incidence of deep vein thrombosis in lower extremities among critically ill patients.
To investigate how many critically ill patients developed deep vein thrombosis (DVT) during their admission to intensive care units (ICU) and to compare the characteristics of patients with and without deep vein thrombosis. Critically ill patients are a high-risk group for deep vein thrombosis because they typically have multiple risk factors, such as prolonged immobility, mechanical ventilation and old age. A prospective observational study was employed. The subjects were 90 patients who were older than 18 years of age, who were admitted to an intensive care unit for more than five days and were not provided any prophylactic measures. Data were collected at a university hospital for five months. A duplex scan was performed on day 2.4 on average and repeated between days 5-7 to diagnose deep vein thrombosis. The iliac, femoral, popliteal and tibial veins were examined by compression and colour Doppler methods of the duplex scan by one technician. Age, gender and body mass index were significant factors for deep vein thrombosis development (p < 0.05). Ten patients (11.1%) developed deep vein thrombosis during their stay in the intensive care units. The incidence was lower than in Western studies in which patients were not provided prophylaxis, but may increase with an extended observation period as in previous studies. The results of this study could allow ICU nurses to recognise the DVT incidence in critically ill patients. This result could lead to more active prevention and monitoring of DVT by ICU nurses, especially for high-risk patients, such as older or obese patients.


Inflectional morphology in German Williams syndrome.
In a recent paper, Clahsen and Almazan (1998) reported a dissociation between unimpaired regular and impaired irregular past tense morphology in English Williams syndrome (WS). Our aim is to investigate whether these findings carry over to another language with different morphological systems. We present data on regular and irregular participles and noun plurals from 2 German WS subjects and 10 controls matching in mental age. For noun plurals, regular morphology is intact in WS, whereas irregular forms are impaired. A similar dissociation is observed for participles: while regular inflection is unimpaired, WS subjects, unlike controls, apply the regular suffix incorrectly to frequent irregular verbs. We discuss our findings against the current debate between connectionist and dualistic approaches to the language faculty.


Preparation of collagen/gelatin sponge scaffold for sustained release of bFGF.
Artificial dermis (AD) has been used to regenerate dermis-like tissues in the treatment of full-thickness skin defects, but it takes 2 or 3 weeks to complete dermal regeneration. Our previous study demonstrated that injection of basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres (MS) into the AD accelerates the regeneration of dermis-like tissue. However, injection of gelatin MS before clinical use is complicated and time consuming. This study investigated a new scaffold, in which collagen and gelatin are integrated, and which is capable of sustained bFGF release. We produced collagen/gelatin sponges with a gelatin concentration of 0wt%, 10wt%, 30wt%, and 50wt%. The mean pore size in each sponge decreased with the gelatin concentration. In an in vitro study, proliferation of fibroblasts in each sponge was not significantly different over 7 days of culture. As for in vivo sustained release of bFGF, a radioisotope study demonstrated that retention of bFGF in gelatin 10wt% and 30wt% sponges was significantly larger than that in gelatin 0wt% sponge. The collagen/gelatin sponges were grafted on full-thickness skin defects created on a rabbit ear, and we evaluated regeneration of dermis-like tissue by measuring the amount of hemoglobin and size of dermis-like tissue on histological sections. Seven days after implantation, the amount of hemoglobin in dermis-like tissue in gelatin 10wt% sponge was significantly larger than those in control and gelatin 50wt% sponge. Twenty-eight days after implantation, the area of dermis-like tissue in gelatin 10wt% sponge was significantly larger than those in the other specimens. We conclude that the collagen sponge integrated with 10wt% gelatin has the most potential for sustained release of bFGF and that the combination of collagen/gelatin 10wt% sponge and bFGF is a promising therapeutic modality for the treatment of full-thickness skin defects.


[Is the inverted position of the kidney graft a cause of disease after transplantation?].
The authors explain their experience in a series of 317 consecutive RTs that resulted in renal inversion during transplantation surgery. The likely vascular complications as well as those of the excretory tract are correlated with the above situation of heterotopic graft. No differences have been noted due to placement with regard to necrosis of the ureter; stenosis of the passage, whether distally or at the pyelo-ureteral junction, have occurred in inverted kidneys but at a really low rate (1.7%) in both cases. There has been, however, a higher incidence of arterial thrombosis when the kidney is not inverted. A conclusion can be drawn that it is preeminent to place the kidney with a good vascular arrangement and that, once this is achieved, the tendency is to leave the posterior pelvis which allows to shorten the ureter.


Rett syndrome: model of neurodevelopmental disorders.
Rett syndrome is a neurodevelopmental disorder that primarily affects girls, most of whom have mutations in the transcription regulatory gene MECP2. However, mutations in MECP2 also have been identified in normal carrier female individuals, female individuals with mild learning disabilities and features of Angelman syndrome, and male individuals with Klinefelter syndrome or Rett syndrome-like features, fatal neonatal encephalopathy, and familial X-linked mental retardation with or without motor abnormalities. Therefore, molecular testing should be considered for a wide spectrum of individuals. As such, Rett syndrome remains a clinical diagnosis. In this article, we also discuss three recent developments: (1) the recognition of significant gallbladder dysfunction, especially in those 20 years of age or younger; (2) a clinical trial of folate and betaine, which produced no objective improvement but did yield a subjective increase in attention and interaction; and (3) measurement of cerebrospinal fluid folate levels in a large cohort, which yielded normal values, indicating no need for supplementation.


Thermal management and blood loss during hip arthroplasty.
Perioperative hypotermia is a common, but preventable complication of anaesthesia and surgery. Mild perioperative hypothermia increases the incidence of morbid myocardial outcomes, reduces resistance to surgical wound infections, and prolongs both postanaesthetic recovery and hospitalization. Hypotermia causes a coagulopathy due to inhibition of platelet function. In this short review, we will discuss three studies done in the last 6 years, which explored the influence of perioperative hypotermia and blood loss. All evaluated blood loss during hip arthroplasty and had similar methodologies. Two studies demonstrate that blood loss is increased, especially during surgery, in hypotermic patients while a third study failed to identify any thermal influence on blood loss. The benefits of maintaining perioperative normothermia on blood loss thus remain unclear. We thus continue to recommend that surgical patients be kept normothermic.


[Biomaterials and technologies for vascular grafts: from bench to bedside].
Peripheral artery disease and related revascularization procedures are increasing, due to the aging population and growing incidence of diabetes mellitus. Up to now, autologous saphenous vein is the conduit of choice for peripheral by-pass. Synthetic vascular graft in polyethylene terephthalate (Dacron®) and expanded polytetrafluoroethylene (ePTFE) are used if vein access cannot be obtained. These synthetic grafts are successfully used to replace large diameter vessels, but they fail in small diameters (<6 mm) such as for infragenicular by-pass. Reasons for failure are early thrombosis and late intimal hyperplasia. Novel small-diameter vascular grafts with an acceptable clinical outcome are therefore needed. Here, the main materials and technologies for the manufacturing of vascular grafts and the pathway from bench to bedside are discussed .


De novo design of non-coordinating indolones as potential inhibitors for lanosterol 14-α-demethylase (CYP51).
The development of antifungal drugs that inhibit lanosterol 14-α-demethylase (CYP51) via non-covalent ligand interactions is a strategy that is gaining importance. A series of novel tetraindol-4-one derivatives with 1- and 2-(2,4-substituted phenyl) side chains were designed and synthesized based on the structure of CYP51 and fluconazole. The antifungal activities of these derivatives against eight human pathogenic filamentous fungi and yeast strains were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds 8a-g displayed activity against Candida tropicalis, Candida guilliermondii and Candida parapsilosis with a minimum inhibitory concentration (MIC) value until 8 µg mL(-1), on the other hand compounds 7a-g showed activity against Aspergillus fumigatus with a MIC value of 31.25 µg mL(-1). A molecular modeling study of the binding interactions between compounds 6, 7d, 8g and the active site of MtCYP51 was conducted based on the computational docking results.


[50 years Rodewisch theses--for the beginnings of social-psychiatric reforms in East Germany (GDR)].
The so-called Rodewisch Theses of 1963 demonstrate East German psychiatry's attempts to implement social-psychiatric reforms. To mark their 50th anniversary, this article analyses their emergence, drafting and implementation. It has been known that key requirements could only be fulfilled on a regional basis, the Leipzig University Department of Psychiatry being an outstanding example, although its staff worked rather autonomously of the Rodewisch Theses. The reasons for the different degree of success of these developments in individual areas are manifold, key reasons being the lack of stark political support and of opportunity to discuss shortcomings in mental health care, as in Western Germany, due to political circumstances in particular. There was no strong social basis and support as in Western democracies.


Adaptogenic and in vitro antioxidant activity of flavanoids and other fractions of Argyreia speciosa (Burm.f) Boj. in acute and chronic stress paradigms in rodents.
Argyreia speciosa (sweet) (Burm.f.) Boj. is an Ayurvedic rasayana plant used as an adaptogen. The present study reports the investigations done on the adaptogenic property of ethanol (EtAS; 100 and 200 mg/kg; po), ethyl acetate (EAAS; 100 and 200 mg/kg; po) fraction and flavanoids such as quercetin and kaempferol (25 mg/kg; po) of the root. Immobilization induced acute stress (AS; 3 days) and chronic stress (CS; 7 days) and swimming induced stress models were used to screen the anti-stress effect of the plant fractions and isolated flavanoids. The tested doses of EtAS and isolated flavanoids were able to produce significant effects in normalizing altered serum biochemical parameters and the severity of ulcer in both AS and CS models. Higher dose of EtAS, quercetin and kaempferol (25 mg/kg; po) were found to be significant in restoring the hypertrophy of adrenal gland and atrophy of spleen and thymus gland only in CS model. Greater swimming time was noted in the mice pretreated with tested doses of flavanoids and EtAS. In addition, levels of adrenal ascorbic acid and cortisol were restored compared to stress control group. EtAS exhibited significant scavenging effect of DPPH, hydroxyl radical and LPO. Thus, EtAS, quercetin and kaempferol are capable of increasing the capacity to tolerate non-specific stress in experimental animals, as evident from restoration of large number of parameters in the stress models studied. Bioactivity of EtAS may be due to the synergetic action of isolated flavanoids. Improvement in stress markers may be due its prolong effect of resistance to stress and partly due to free radical scavenging activity.


Effect of backchannel utterances on facilitating idea-generation in Japanese think-aloud tasks.
The relation between backchannel utterance and idea-generation has hardly been studied. Based on preliminary investigations, we formulated a hypothesis that a listener's backchannel utterances facilitate a speaker's idea-generation. This study experimentally manipulated the frequency of backchannel utterances by listeners during speakers' idea-generation for think-aloud tasks. 16 Japanese female undergraduates participated. Analysis indicated that frequent backchannel utterances increased not only the number of ideas generated but also the speaking time for the tasks.


Health as expanding consciousness: seven women living with multiple sclerosis or rheumatoid arthritis.
The meaning of health as expanding consciousness is explored through stories of seven women who developed multiple sclerosis or rheumatoid arthritis during their lives. Using Newman's hermeneutic-dialectic approach, unstructured interviews were conducted over a 2-year period. Analysis and interpretation of narratives concerning person-environment interactions revealed turning points and separate choice points before four new ways of living including finding simple pleasures, being positive, gaining self-control, and self-differentiation, were found. Support for Newman's stages of expanding consciousness and more comprehensive descriptions of self-transcendence in space and time are presented. Implications for theory development and theory-guided practice are offered.


Factors influencing knowledge on completion of treatment among TB patients under directly observed treatment strategy, in selected health facilities in Embu County, Kenya.
The World Health Organization (WHO) promotes the Directly Observed Treatment (DOT) strategy as the standard to increase adherence to Tuberculosis (TB) medication. However, cases of retreatment and Multi Drug Resistant continue to be reported in many parts of Kenya. This study sought to determine the factors influencing the completion of tuberculosis medication among TB patients in Embu County, Kenya. A descriptive cross-sectional study was conducted on a population of tuberculosis patients under DOT attending selected TB treatment clinics in Embu County, in Kenya. One hundred and forty TB patients interviewed within a period of 3 months. Data were analyzed using SPSS version 17.0 and included Bivariate and Multivariate Analysis. The level of significance was p≤ 0.05. The male and female participants were 61.4% and 38.6% respectively. The mean age of the respondents was 35±31.34-39.3 years. For the majority (52%) of the participants, the highest level of education was primary education. The unemployed participants formed the highest number of the respondent in the study (73%). The majorities (91.4%0) of the respondents were under the home-based DOT strategy (91.4%, 95% C.I: 85.5-95.5). Bivariate analysis using Chi-square showed that the level of education (p=0.003), patients feeling uncomfortable during supervision (p=0.01), and knowledge regarding the frequency of taking medication (p=0.004) were all significantly associated with knowledge regarding the importance of completion of medication. However, none of these factors was significant after multivariate analysis. Most participants did not know the importance of completion of medication. TB programs should come up with better ways to educate TB patients on the importance of supervision and treatment completion during the treatment of TB. The education programs should focus on influencing the attitudes of patients and creating awareness about the importance of treatment completion. The TB programs should be designed towards eliminating the factors influencing the completion of TB medication.


A laparoscopic triple stapling technique that facilitates anterior resection for rectal cancer.
A new technique that facilitates laparoscopic anterior resection is described. The technique is a modification of a triple stapling technique that the authors currently use for conventional anterior resection of the mid- and low-rectal cancers. The new laparoscopic technique may reduce the risk of staple line or port site recurrence.


Breakthrough Pain in Patients with Lung Cancer. A Secondary Analysis of IOPS MS Study.
To characterize breakthrough cancer pain (BTcP) in patients with lung cancer. This was a secondary analysis of multicenter study of patients with BTcP. Background pain intensity and opioid dose were recorded. The number of BTcP episodes, their intensity, predictability, onset, duration and interference with daily activities were collected. Opioids used for BTcP, the mean time to meaningful pain relief after taking medication, satisfaction and adverse effects were assessed. 1087 patients with lung cancer were examined. In comparison with other tumors, patients with lung cancer showed: higher background pain intensity (p = 0.006), lower opioid doses (p = 0.005), higher intensity of BTcP (p = 0.005), movement (79.5%) and cough (8.2%), as principal triggers for predictable BTcP (p < 0.009), larger BTcP interference with daily activity (p = 0.0001), higher use of adjuvants (p = 0.0001). No relevant differences in the other parameters examined were found. Patients with lung cancer have their own peculiarities, including higher basal and BTcP pain intensity and the use of more adjuvant drugs for background pain. The most frequent triggers for predictable BTcP are movement and cough. Future studies should be performed to analyze the prevalence of BTcP in patients with different lung cancers as well as the optimal management strategy for background pain and BTcP.


Temperature and pressure tuneable swollen bicontinuous cubic phases approaching nature's length scales.
Bicontinuous cubic structures offer enormous potential in applications ranging from protein crystallisation to drug delivery systems and have been observed in cellular membrane structures. One of the current bottlenecks in understanding and exploiting these structures is that cubic scaffolds produced in vitro are considerably smaller in size than those observed in biological systems, differing by almost an order of magnitude in some cases. We have addressed this technological bottleneck and developed a methodology capable of manufacturing highly swollen bicontinuous cubic membranes with length scales approaching those seen in vivo. Crucially, these cubic systems do not require the presence of proteins. We have generated highly swollen Im3m symmetry bicontinuous cubic phases with lattice parameters of up to 480 Å, composed of ternary mixtures of monoolein, cholesterol and negatively charged lipid (DOPS or DOPG) and we have been able to tune their lattice parameters. The swollen cubic phases are highly sensitive to both temperature and pressure; these structural changes are likely to be controlled by a fine balance between lipid headgroup repulsions and lateral pressure in the hydrocarbon chain region.


Cryptosporidiosis in HIV-positive patients and related risk factors: A systematic review and meta-analysis.
Cryptosporidium is one of the major causes of diarrhea in HIV-positive patients. The aim of this study is to systematically review and meta-analyze the prevalence of Cryptosporidium in these patients. PubMed, Science Direct, Google Scholar, Web of Science, Cochrane and Ovid databases were searched for relevant studies dating from the period of 1 January 2000 to 31 December 2017. Data extraction for the included studies was performed independently by two authors. The overall pooled prevalence was calculated and subgroup analysis was performed on diagnostic methods, geographical distribution and study population. Meta-regression was performed on the year of publication, proportion of patients with diarrhea, and proportion of patients with CD4 < 200 cells/mL. One hundred and sixty-one studies and 51,123 HIV-positive participants were included. The overall pooled prevalence of Cryptosporidium infection in HIV-positive patients was 11.2% (CI95%: 9.4%-13.0%). The pooled prevalence was estimated to be 10.0% (CI95%: 8.4%-11.8%) using staining methods, 13.5% (CI95%: 8.9%-19.8%) using molecular methods, and 26.3% (CI95%: 15.0%-42.0%) using antigen detection methods. The prevalence of Cryptosporidium in HIV patients was significantly associated with the country of study. Also, there were statistical differences between the diarrhea, CD4 < 200 cells/mL, and antiretroviral therapy risk factors with Cryptosporidiosis. Thus, Cryptosporidium is a common infection in HIV-positive patients, and safe water and hand-hygiene should be implemented to prevent cryptosporidiosis occurrence in these patients.


Biological Evaluation of Xanthene and Thioxanthene Derivatives as Antioxidant, Anticancer, and COX Inhibitors.
Xanthene and thioxanthene analogues have been investigated for their potential as anticancer and anti-inflammatory agents. Additionally, cysteine analogues have been found to possess antioxidant, anti-inflammatory, and anticancer activities due to their role in cellular redox balance, scavenging of free radicals, and involvement in nucleophilic reactions and enzyme binding sites. In this study, we synthesized a library of tertiary alcohols derived from xanthene and thioxanthene, and further, some of these compounds were coupled with cysteine. The objective of this research was to explore the potential anticancer, antioxidant, and anti-inflammatory activities of the synthesized compounds. The synthesized compounds were subjected to test for anticancer, antioxidant, and anti-inflammatory activities. Results indicated that compound 3 exhibited excellent inhibition activity (IC50 = 9.6 ± 1.1 nM) against colon cancer cells (Caco-2), while compound 2 showed good inhibition activity (IC50 = 161.3 ± 41 nM) against hepatocellular carcinoma (Hep G2) cells. Compound 4 demonstrated potent antioxidant inhibition activity (IC50 = 15.44 ± 6 nM), and compound 7 exhibited potent anti-inflammatory activity with cyclooxygenase-2 (COX-2) inhibition IC50 (4.37 ± 0.78 nM) and high selectivity for COX-2 (3.83). In conclusion, certain synthesized compounds displayed promising anticancer activity and anti-inflammatory effects. Nevertheless, additional research is necessary to create more analogues, develop a more distinct comprehension of the structure-activity relationship (SAR), and perform in vivo experiments to evaluate the pharmacokinetic and pharmacodynamic characteristics of the compounds under examination. Such research may pave the way for the development of novel therapeutic agents with potential applications in cancer and inflammatory diseases.


Medication Adherence and Coping with Disease in Patients from a Neurological Clinic: An Observational Study.
Medication non-adherence is a huge concern for the medical community. For chronic, especially neurological diseases, taking medication is a central pillar of treatment. To improve adherence to these oftentimes complex medication regimens, the construct needs to be understood in more depth. The aim of this study was to investigate associations between adherence with sociodemographics, clinical variables, and coping in neurological patients. The sample consisted of 545 patients from a German neurological clinic. Adherence was assessed with the Stendal Adherence to Medication Score (SAMS). Patients were grouped as completely adherent (SAMS = 0), non-adherent (upper 25% of the sample), and moderately adherent. Associations with coping were assessed using the Essen Coping Questionnaire. Medication adherence was low compared to other non-neurological patient samples. Differences between adherence groups were found regarding gender and facets of coping, namely "trivialisation, wishful thinking and defence" and "finding of inner stability". Interventions to improve medication adherence should focus on facets of coping with disease, increasing acceptance of disease, willpower, and confidence in treatment.


Characteristics of the locomotor-like muscle activity during orthotic gait in paraplegic persons.
We previously found that orthotic gait training can induce 'locomotor-like' coordinated muscle activity of the paralyzed lower limb in persons with spinal cord injury (SCI). The purpose of the present study was to characterize the locomotor-like muscle activity based on data obtained from electromyographic recordings and motion analysis during orthotic gait in nine motor complete SCI subjects. Seven of nine subjects showed a common EMG activation pattern mainly in the ankle (soleus: Sol) and hip extensor (biceps femoris: BF) muscles. The locomotor-like muscle activity was well synchronized with the gait cycle, namely, the EMG amplitude of both Sol and BF muscle had common temporal relationships with the ground reaction force, and hip and ankle joint motions. While the presence or absence of the EMG activity during orthotic gait was consistent with those of mechanically-induced stretch reflex, the duration and amount area of the locomotor-like muscle activity were significantly longer than those of the stretch reflex in the Sol muscle. Moreover, the Sol EMG magnitude had strong relevance to hip as well as ankle angular velocities. These results indicate that the locomotor-like muscle activity during orthotic gait is not a mere reflex response, but includes an activity of the central pattern generator (CPG) and its interaction with afferent inputs. Orthotic gait training for complete SCI persons might have a potential to activate the spinal locomotor center.


Injection therapy for impotence.
Injection of vasoactive drugs is an effective form of treatment for selected patients with impotence from virtually all causes. The two most commonly employed drugs in the United States are either papaverine alone or various combinations of papaverine and phentolamine. Patients with organic and mixed impotence are best suited for injection treatment, but selected patients with psychogenic impotence also benefit from therapy. After the patient is selected for injection therapy, he undergoes a series of trial injections in the physician's office. The incidence of priapism will be minimized if the initially administered doses are low and the patient is titrated to an appropriate dose level. Uncontrolled trials have revealed that injection treatment produces a satisfactory erection in 65 to 100 per cent of patients for a follow-up period of as long as 2 years with minimal side effects, but the dropout rate is high. If priapism does occur, it almost always responds readily to treatment with aspiration, low doses of an alpha-adrenergic agent, or both. The other common side effects are bruising or ecchymosis and nodule formation at the injection site. This latter complication has not been noted to cause significant abnormal penile curavature necessitating cessation of the program.


Amphotericin B-induced hepatorenal failure in cystic fibrosis.
Although nephrotoxicity is a common and well-recognized side effect of amphotericin B, hepatotoxicity is rare. We report on a 9-year-old girl with cystic fibrosis who developed fulminant renal and hepatic dysfunction following a short course of intravenous amphotericin B for a suspected aspergillus infection, although she did not have clinical evidence of invasive aspergillosis. The toxicity became apparent after changing to liposomal amphotericin. This association of renal and hepatotoxicity with liposomal amphotericin B has not previously been reported in children.


Evaluation of the importance of centrifugation as a component of zinc sulfate fecal flotation examinations.
Fifty canine fecal samples were evaluated by five flotation procedures to compare the sensitivity of the zinc sulfate (ZnSO4) centrifugation flotation test with ZnSO4 flotation tests using benchtop incubation during the flotation period. One or more parasite species were detected in 40 samples. Results showed that centrifugation with ZnSO4 solution was significantly more likely to detect a positive sample than benchtop procedures. The difference in procedures was due primarily to increased detection of Trichuris eggs and Giardia cysts by centrifugal flotation. No significant difference was seen in the ability of benchtop procedures to detect positive samples when tests sat either for 5 or 10 minutes before examination.


Tandem addition of trialkyl phosphites to alpha,beta-unsaturated imines: a comparison with silylated phosphites.
Trialkyl phosphites were evaluated for addition reactions to alpha,beta-unsaturated imines. An acidic medium is required to allow consecutive 1,4- and 1,2-addition to occur. In this manner, 3-phosphonyl-1-aminophosphonates, phosphonic acid analogues of glutamate, are obtained in good yields (32-90%). The reaction is mainly influenced by the steric bulk of the nitrogen substituent: less steric N-substituents lead to better yields of the tandem adducts.


Epithelial barrier function and immunity in asthma.
The bronchial epithelium is constantly exposed to a wide range of environmental materials present in inhaled air, including noxious gases and anthropogenic and natural particulates, such as gas and particles from car emissions, tobacco smoke, pollens, animal dander, and pathogens. As a fully differentiated, pseudostratified mucociliary epithelium, the bronchial epithelium protects the internal milieu of the lung from these agents by forming a physical barrier involving adhesive complexes and a chemical barrier involving secretion of mucus, which traps inhaled particles that can be cleared by the mucociliary escalator. It is a testament to the effectiveness of these two barriers that most environmental challenges are largely overcome without the need to develop an inflammatory response. However, as the initial cell of contact with the environment, the bronchial epithelium also plays a pivotal role in immune surveillance and appropriate activation of immune effector cells and antigen presenting cells in the presence of pathogens or other danger signals. Thus, the bronchial epithelium plays a central role in controlling tissue homeostasis and innate immunity. This review will discuss these barrier properties and how dysregulation of these homeostatic mechanisms can contribute to disease pathologies such as asthma.


Lignin changes after steam explosion and laccase-mediator treatment of eucalyptus wood chips.
Eucalyptus globulus chips were steam exploded followed by treatment with a laccase-mediator system (LMS) under different experimental conditions. Removal of hemicelluloses and, to a lesser extent, lignin was observed. Thermogravimetic analyses of whole meal obtained from chips before and after steam explosion indicated an increase in lignin degradation temperature due to lignin condensation. In contrast, application of LMS treatment caused a reduction in lignin and polysaccharide degradation temperatures. Lignins were isolated from wood samples before and after each treatment and analyzed by 2D NMR and (13)C NMR. An increase in carboxyl and phenolic hydroxyl groups and a significant decrease in β-O-4 structures were found in steam-exploded samples. The most relevant changes observed after laccase treatment were increased secondary OH and degree of condensation.


Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee.
Simian immunodeficiency virus of chimpanzees (SIVcpz), the progenitor of human immunodeficiency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpanzees (Pan troglodytes). Surprisingly, however, similar findings have not been reported for chimpanzees experimentally infected with SIVcpz in captivity, raising questions about the intrinsic pathogenicity of this lentivirus. Here, we report progressive immunodeficiency and clinical disease in a captive western chimpanzee (P. t. verus) infected twenty years ago by intrarectal inoculation with an SIVcpz strain (ANT) from a wild-caught eastern chimpanzee (P. t. schweinfurthii). With sustained plasma viral loads of 105 to 106 RNA copies/ml for the past 15 years, this chimpanzee developed CD4+ T cell depletion (220 cells/μl), thrombocytopenia (90,000 platelets/μl), and persistent soft tissue infections refractory to antibacterial therapy. Combination antiretroviral therapy consisting of emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), and dolutegravir (DTG) decreased plasma viremia to undetectable levels (<200 copies/ml), improved CD4+ T cell counts (509 cell/μl), and resulted in the rapid resolution of all soft tissue infections. However, initial lack of adherence and/or differences in pharmacokinetics led to low plasma drug concentrations, which resulted in transient rebound viremia and the emergence of FTC resistance mutations (M184V/I) identical to those observed in HIV-1 infected humans. These data demonstrate that SIVcpz can cause immunodeficiency and other hallmarks of AIDS in captive chimpanzees, including P. t. verus apes that are not naturally infected with this virus. Moreover, SIVcpz-associated immunodeficiency can be effectively treated with antiretroviral therapy, although sufficiently high plasma concentrations must be maintained to prevent the emergence of drug resistance. These findings extend a growing body of evidence documenting the immunopathogenicity of SIVcpz and suggest that experimentally infected chimpanzees may benefit from clinical monitoring and therapeutic intervention.


Phase diagram and critical behavior of the square-lattice Ising model with competing nearest-neighbor and next-nearest-neighbor interactions.
Using the parallel tempering algorithm and graphics processing unit accelerated techniques, we have performed large-scale Monte Carlo simulations of the Ising model on a square lattice with antiferromagnetic (repulsive) nearest-neighbor and next-nearest-neighbor interactions of the same strength and subject to a uniform magnetic field. Both transitions from the (2x1) and row-shifted (2x2) ordered phases to the paramagnetic phase are continuous. From our data analysis, re-entrance behavior of the (2x1) critical line and a bicritical point which separates the two ordered phases at T=0 are confirmed. Based on the critical exponents we obtained along the phase boundary, Suzuki's weak universality seems to hold.


On the cause and nature of C9-related heterogeneity of terminal complement complexes generated on target erythrocytes through the action of whole serum.
The binding of C8 and C9 from human serum to target erythrocytes was quantified, and the molecular stoichiometries of C9:C8 within terminal C5b-9(m) complexes were determined. Low doses of serum generated terminal complexes with mean C9:C8 ratios of 2 to 3:1, whereas complexes generated by highest serum doses harbored an average of six to eight C9/C8 molecules. From the collective biochemical and ultrastructural data, we concluded that heterogeneous populations of terminal complexes regularly form on target membranes; those containing high numbers of C9 molecules (greater than or equal to six to eight) exhibit the structure of the classical "lesion", whereas those containing low numbers of C9 do not exhibit this typical structure, although they probably still function as small pores. A major cause for this heterogeneity of the lesions derives from shortage of C9, which is naturally present in a 2 to 1 molar ratio relative to C8 in serum. Generation of terminal complexes harboring high numbers of C9 on erythrocyte membranes is possible in spite of this natural shortage because SC5b-9 does not form in the fluid phase to compete for C9 binding. If interrupted, the process of C9-C9 oligomerization cannot be recontinued, and "incomplete" C5b-9 complexes are unable to bind additional C9 upon reincubation with this component. The demonstrated heterogeneity of terminal complexes with respect to their C9 content may explain the functional heterogeneity of complement lesions observed previously by other investigators.